HMGA and Cancer

Fedele, Monica; Fusco, Alfredo

doi:10.1016/j.bbagrm.2009.11.007

Cited by 126 publications

(145 citation statements)

References 106 publications

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“…HMGA1 and HMGA2 positively regulate ATM expression It is well known that HMGA proteins positively or negatively regulate the transcriptional activity of several genes (Fedele et al, 2001a, b;Fusco and Fedele, 2007;Fedele and Fusco, 2010). Therefore, we evaluated the possible role of HMGA proteins in the regulation of ATM expression (Figure 2).…”

Section: Hmga2 Interacts With and Is Phosphorylated By Atmmentioning

confidence: 99%

“…HMGAs are involved in several cellular processes such as gene and micro-RNA expression, chromatin and nucleosome remodeling, DNA replication, apoptosis and DNA repair (Wood et al, 2000;Reeves and Adair, 2005;Fusco and Fedele, 2007;Fedele and Fusco, 2010). HMGAs also has a causal role in cellular transformation (Wood et al, 2000), mainly through the regulation of expression of genes and micro-RNA involved in the control of cellular proliferation, invasion and apoptosis (Reeves and Adair, 2005;Fusco and Fedele, 2007;Fedele and Fusco, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…HMGAs also has a causal role in cellular transformation (Wood et al, 2000), mainly through the regulation of expression of genes and micro-RNA involved in the control of cellular proliferation, invasion and apoptosis (Reeves and Adair, 2005;Fusco and Fedele, 2007;Fedele and Fusco, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Expression of both HMGA genes is restricted to the embryogenesis, resulting low or absent in normal adult tissues (Zhou et al, 1995;Chiappetta et al, 1996), while their overexpression is commonly found in almost all human malignant neoplasias, representing a poor prognostic marker correlated with the presence of metastasis, reduced survival and resistance to anticancer therapies (Fusco and Fedele, 2007;Fedele and Fusco, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, based on the widely described role of HMGAs in the regulation of gene expression (Reeves and Adair, 2005;Fusco and Fedele, 2007;Fedele and Fusco, 2010), we investigated their ability to bind and regulate the ATM gene promoter. Our results indicate that HMGAs positively regulate ATM expression and that ATM kinase activity on HMGA proteins can enhance their transcriptional activity on this promoter, activating a HMGA-dependent positive feedback loop in response to DNA damage.…”

Section: Introductionmentioning

confidence: 99%

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HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents

et al. 2011

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DNA-damaging therapies represent a keystone in cancer treatment. Unfortunately, many tumors often relapse because of a group of cancer cells, which are resistant to conventional therapies. High-mobility group A (HMGA) proteins has a key role in cell transformation, and their overexpression is a common feature of human malignant neoplasias, representing a poor prognostic index often correlated to anti-cancer drug resistance. Our previous results demonstrated that HMGA1 is a substrate of ataxiatelangiectasia mutated (ATM), the main cellular sensor of genotoxic stress. Here we also report thatHMGA2, the other member of the HMGA family, is a novel substrate of ATM. Interestingly, we found that HMGA proteins positively regulate ATM gene expression. Moreover, induction of ATM kinase activity by DNA-damaging agents enhances HMGA-dependent transcriptional activation of ATM promoter, suggesting that ATM expression is modulated by a DNA-damage-and HMGA-dependent positive feedback loop. Finally, inhibition of HMGA expression in mouse embryonic fibroblasts and in cancer cells strongly reduces ATM protein levels, impairing the cellular DNA-damage response and enhancing the sensitivity to DNA-damaging agents. These findings indicate this novel HMGA-ATM pathway as a new potential target to improve the effectiveness of conventional anti-neoplastic treatments on the genotoxic-drug resistant cancer cells.

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Section: Hmga2 Interacts With and Is Phosphorylated By Atmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents

et al. 2011

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Nanoparticle‐mediated HMGA1 Silencing Promotes Lymphocyte Infiltration and Boosts Checkpoint Blockade Immunotherapy for Cancer

Wang

Song

et al. 2018

Adv Funct Materials

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For most cancer types, only a minority of cancer patients respond to checkpoint inhibition therapy. T lymphocyte infiltration is critically important for checkpoint blockade immunotherapy. High expression of high mobility group protein A1 (HMGA1) is observed in rapidly proliferating neoplastic cells, and is reported to contribute to the immunosuppressive microenvironment in the tumor. Herein, whether the silencing of HMGA1 using a nanoparticle (NP) approach could promote T lymphocyte infiltration into the tumor, and sensitize tumors to checkpoint inhibitor therapy in several orthotopic murine cancer models, which has high levels of HMGA1 but little T lymphocyte infiltration, is investigated. Selectively silencing HMGA1 using a lipid-protamine-hyaluronic acid-siHMGA1 (LPH-siHMGA1) NP system greatly enhances the lymphocyte infiltration in the tumor. Furthermore, the combination of LPH-siHMGA1 and a locally expressed PD-L1 inhibitor system, a lipid-protamine-DNA NP loaded with plasmid encoding the PD-L1 trap fusion protein, significantly inhibits the tumor growth and prolonged survival. LPH-siHMGA1 also decreased the content of stem cells in the tumor. These findings highlight the potential of targeting HMGA1, especially using a nano approach, in the combination with cancer immunotherapy, and provide a strategy for broadening the application and enhancing the efficacy of checkpoint inhibitors.

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Mycalol: A Natural Lipid with Promising Cytotoxic Properties against Human Anaplastic Thyroid Carcinoma Cells

et al. 2013

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Aus dem Südlichen Eismeer: Zellen des humanen anaplastischen Schilddrüsenkarzinoms (ATC), die ein Antisense‐ Konstrukt gegen HMGA‐Proteine stabil exprimieren, wurden in einem phänotypischen Assay zum Screening mariner Extrakte eingesetzt. Dieser gezielte Suchansatz führte zur Isolierung und Identifizierung des neuartigen polyoxygenierten linearen Lipids 1, das selektiv gegen von ATC abgeleitete Tumorzelllinien wirkt.

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HMGA and Cancer

Cited by 126 publications

References 106 publications

HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents

HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents

Nanoparticle‐mediated HMGA1 Silencing Promotes Lymphocyte Infiltration and Boosts Checkpoint Blockade Immunotherapy for Cancer

Mycalol: A Natural Lipid with Promising Cytotoxic Properties against Human Anaplastic Thyroid Carcinoma Cells

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